We are requesting $500,000 to purchase a massively parallel DNA sequencer for use by the Columbia University community and collaborators at other institutions. There is no comparable instrument available on any of the campuses of Columbia University. A single sequencing run on this instrument will achieve the equivalent of over 100 sequencing runs on each of Columbia University's currently available 2 instruments, thus dramatically expanding the scope of research programs. [unreadable] This instrument will be used by a broad range of NIH-funded investigators. Projects range from comparative genomics of microorganisms to identify genes and genome regions associated with distinct forms of pathogenicity, a metagenomics study of the effect of influenza virus infection on bacterial flora, global basic research studies of motifs involved in splicing, transcription, and of tissue specific miRNA species, and populations of sequences in directed enzyme evolution; much of the projected use will involve identification of genetic changes involved in a wide range of diseases from glomerulonephritis to diabetes, neuropsychiatric disorders to alopecia, lymphoma to arrhythmias, with results anticipated to provide insight into the mechanism of disease, diagnosis, prognosis and treatment. [unreadable] The instrument, housed in the Genome Center, will be run by staff well experienced with DNA sequencing and methods development, and supported by all required ancillary instruments and computational resources. Columbia University has demonstrated its commitment to the maintenance and operation of this instrument by pledging support for warranty extension and a technician covering the first year and a half of operation, following which the instrument will be supported by user fees. Given the large number of biomedical investigators on the campuses of Columbia University, the presence of such an instrument would have a significant impact on NIH-funded research. [unreadable] [unreadable] [unreadable]